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| Status |
Public on Oct 21, 2016 |
| Title |
Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (single cell RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement.
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| Overall design |
Differentiated naïve human embryonic stem cells and naïve human embryonic stem cells at different passages (Exp1 for late passage, Exp2 for early passage) were subjected to single cell RNA sequencing by the Fluidigm C1 Single-Cell Auto Prep System.
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| Contributor(s) |
Sahakyan A, Kim R, Chronis C, Sabri S, Bonora G, Theunissen TW, Kuoy E, Langerman J, Clark AT, Jaenisch R, Plath K |
| Citation(s) |
27989770 |
| Submission date |
Sep 22, 2016 |
| Last update date |
Nov 19, 2020 |
| Contact name |
Kathrin Plath |
| Organization name |
UCLA
|
| Department |
Biological Chemistry
|
| Lab |
BSRB 390B
|
| Street address |
615 Charles E. Young Drive South
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095-1737 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (288)
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| This SubSeries is part of SuperSeries: |
| GSE87239 |
Human naive pluripotent stem cells exhibit X chromosome dampening and X-inactivation |
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| Relations |
| BioProject |
PRJNA343935 |
| SRA |
SRP090309 |
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